Ectoparasite infestation of animals is of health and economic concern because ectoparasites are known to cause and/or transmit a variety of diseases. Ectoparasites cause and/or carry infectious agents that cause, for example, allergy dermatitis, anemia, murine typhus, plague and tapeworm. In addition, ectoparasites, in particular fleas, are a problem for animals maintained as pets because the infestation becomes a source of annoyance for the pet owner who may find his or her home generally contaminated with ectoparasites which feed on the pets. As such, ectoparasites are a problem not only when they are on an animal but also when they are in the general environment of the animal.
In addition, ectoparasite bites, such as flea bites, can cause a hypersensitive response in animals. For example, hypersensitive responses to flea bites is manifested in a disease called flea allergy dermatitis (FAD). Hypersensitivity refers to a state of altered reactivity in which an animal, having been previously exposed to a compound, exhibits an allergic response to the compound upon subsequent exposures. There are four major types of hypersensitive responses (described in detail in, for example, Janeway et al., in Immunobiology, Garland Publishers, New York, N.Y., 1994). FAD can have manifestations of both immediate and delayed-type hypersensitivity. Typically, an immediate hypersensitive response in an animal susceptible to FAD includes wheal formation at the site of a bite. Such wheals can develop into a papule with a crust, representative of delayed-type hypersensitivity.
Foreign compounds that induce symptoms of immediate and/or delayed hypersensitivity are herein referred to as allergens. The term "allergen" primarily refers to foreign compounds capable of causing an allergic response. The term can be used interchangeably with the term "antigen," especially with respect to a foreign compound capable of inducing symptoms of immediate and/or delayed hypersensitivity. Factors that influence an animal's susceptibility to an allergen can include a genetic component and/or environmental exposure to an allergen. Animals can be de-sensitized to an allergen by repeated injections of the allergen to which an animal is hypersensitive.
The medical and veterinary importance of ectoparasite infestation has prompted the development of reagents capable of controlling ectoparasite infestation. Commonly encountered methods to control ectoparasite infestation are generally focussed on use of insecticides in formulations such as sprays, shampoos, dusts, dips, or foams, or in pet collars. While some of these products are efficacious, most, at best, offer protection of a very limited duration. Furthermore, many of the methods are often not successful in reducing ectoparasite populations on the pet for one or more of the following reasons: (1) failure of owner compliance (frequent administration is required); (2) behavioral or physiological intolerance of the pet to the pesticide product or means of administration; and (3) the emergence of ectoparasite populations resistant to the prescribed dose of pesticide. Additional anti-ectoparasite products include chemical drugs that can, for example, affect the development of ectoparasitic larvae.
Prior investigators have determined that histamine can be released in mammals in response to ectoparasite bites. A variety of biological mechanisms can be responsible for the release of histamine in an animal. Only mammalian histamine releasing factors, however, have been defined; see, for example, Wanstall et al., Toxicon 12:649-655, 1974; Toki et al., Biomedical Research 9(1):75-79, 1988; Toki et al., Biomedical Research 9(1):421-428, 1988; Liao et al., J. Allergy Clin. Immunol. 86:894-901, 1990; and Matuszek et al., Natural Toxins 2:36-43, 1994.
Thus, there remains a need to identify an efficacious compound capable of reducing ectoparasite burden on animals, desensitizing animals to ectoparasite allergens and/or reducing inflammation in an animal.